Cancer Science最新文献_第3页

Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-25 DOI: 10.1111/cas.70018

Hiroki Sonoda, Takeshi Iwasaki, Shin Ishihara, Taro Mori, Yasuharu Nakashima, Yoshinao Oda

{"title":"Impact of Tertiary Lymphoid Structure on Prognosis and Tumor Microenvironment in Undifferentiated Pleomorphic Sarcoma.","authors":"Hiroki Sonoda, Takeshi Iwasaki, Shin Ishihara, Taro Mori, Yasuharu Nakashima, Yoshinao Oda","doi":"10.1111/cas.70018","DOIUrl":"https://doi.org/10.1111/cas.70018","url":null,"abstract":"Undifferentiated pleomorphic sarcoma (UPS) has a favorable objective response rate to anti-PD-1 drugs compared with other sarcomas. Tertiary lymphoid structure (TLS) is a favorable prognostic factor and a biomarker for immune checkpoint inhibitors (ICIs). Nevertheless, there are limited data on the tumor microenvironment (TME) to support a good response to ICIs in sarcoma. Therefore, this study was conducted to investigate the impact of TLS on prognosis and TME. A total of 52 of UPS with wide resection were divided into intratumoral TLS, extratumoral TLS, and without TLS groups. Survival analysis and immunohistochemistry were performed to evaluate immune cells and immune checkpoint molecules, and multiplexed immunofluorescence was conducted to evaluate T-cell exhaustion among the three groups. TLS was detected in 34 cases (65%), including 23 intratumoral TLS (44%) and 11 extratumoral TLS (21%) cases. Patients with TLS had significantly longer overall survival than those without TLS (log rank p = 0.020). The intratumoral TLS group had a significantly higher number of immune cells and higher expression of PD-L1 and IDO-1 than the without TLS group. Progenitor-exhausted T cells were also observed in patients with UPS. In conclusion, these findings could help predict prognosis in patients with UPS. TLS was demonstrated to be a favorable prognostic factor in patients with UPS. Intratumoral TLS may be a biomarker for the response to ICIs, especially anti-PD-1 drugs.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143505256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Loss of Tapasin in Tumors Potentiates T-Cell Recognition and Anti-Tumor Effects of Immune Checkpoint Blockade.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-24 DOI: 10.1111/cas.70027

Keigo Moniwa, Serina Tokita, Toshiyuki Sumi, Hiroshi Saijo, Shintaro Sugita, Kotomi Arioka, Yoshihiko Hirohashi, Hirofumi Chiba, Takayuki Kanaseki, Toshihiko Torigoe

引用次数: 0

Novel CHI3L1-Associated Angiogenic Phenotypes Define Glioma Microenvironments: Insights From Multi-Omics Integration.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-24 DOI: 10.1111/cas.70028

Yu-Hang Zhao, Yu-Xiang Cai, Zhi-Yong Pan, Feng Tang, Chao Ma, Ze-Fen Wang, Gang Li, Hang Chang, Su-Fang Tian, Zhi-Qiang Li

{"title":"Novel CHI3L1-Associated Angiogenic Phenotypes Define Glioma Microenvironments: Insights From Multi-Omics Integration.","authors":"Yu-Hang Zhao, Yu-Xiang Cai, Zhi-Yong Pan, Feng Tang, Chao Ma, Ze-Fen Wang, Gang Li, Hang Chang, Su-Fang Tian, Zhi-Qiang Li","doi":"10.1111/cas.70028","DOIUrl":"https://doi.org/10.1111/cas.70028","url":null,"abstract":"The CHI3L1 signaling pathway significantly influences glioma angiogenesis, but its role in the tumor microenvironment (TME) remains elusive. We propose a novel CHI3L1-associated vascular phenotype classification for glioma through integrative analyses of multiple datasets with bulk and single-cell transcriptome, genomics, digital pathology, and clinical data. We investigated the biological characteristics, genomic alterations, therapeutic vulnerabilities, and immune profiles within these phenotypes through a comprehensive multi-omics approach. We constructed the vascular-related risk (VR) score based on CHI3L1-associated vascular signatures (CAVS) identified by machine learning algorithms. Utilizing unsupervised consensus clustering, gliomas were stratified into three distinct vascular phenotypes: Cluster A, marked by high vascularization and stromal activation with a relatively low levels of tumor-infiltrating lymphocytes (TILs); Cluster B, characterized by moderate vascularization and stromal activity, coupled with a high density of TILs; and Cluster C, defined by low vascularization and sparse immune cell infiltration. We observed that the CAVS effectively indicated glioma-associated angiogenesis and immune suppression by single-cell RNA-seq analysis. Moreover, the high-VR-score group exhibited enhanced angiogenic activity, reduced immune response, resistance to immunotherapy, and poorer clinical outcomes. The VR score independently predicted glioma prognosis and, combined with a nomogram, provided a robust clinical decision-making tool. Potential drug prediction based on transcription factors for high-risk patients was also performed. Our study reveals that CHI3L1-associated vascular phenotypes shape distinct immune landscapes in gliomas, offering insights for optimizing therapeutic strategies to improve patient outcomes.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

NEK2 Control of Esophageal Squamous Cell Carcinoma Growth Based on Circadian Oscillation.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-18 DOI: 10.1111/cas.16461

Boning Zeng, Chao Sun, Nan Li, Qiuling Chen, Manni Rao, Kai Li, Xiaodi Liu, Shouxia Xie, Jiwu Cheng, Shaoxiang Wang, Xiao Wang

{"title":"NEK2 Control of Esophageal Squamous Cell Carcinoma Growth Based on Circadian Oscillation.","authors":"Boning Zeng, Chao Sun, Nan Li, Qiuling Chen, Manni Rao, Kai Li, Xiaodi Liu, Shouxia Xie, Jiwu Cheng, Shaoxiang Wang, Xiao Wang","doi":"10.1111/cas.16461","DOIUrl":"https://doi.org/10.1111/cas.16461","url":null,"abstract":"Esophageal squamous cell carcinoma (ESCC) is a globally prevalent malignancy known for its aggressive nature and unfavorable outcomes. Identifying new biomarkers is crucial for the early detection and improved prognostication of ESCC. The circadian clock and NIMA-related kinase 2 (NEK2) are pivotal in cancer development. While the impact of circadian rhythm disruptions on ESCC progression is evident, the specific contribution of NEK2 to these changes is not well understood. Our study discovered NEK2 as a consistently differentially expressed gene across multiple datasets, with elevated expression in ESCC tissues. Notably, NEK2 overexpression was linked to increased ESCC cell proliferation, whereas its inhibition led to reduced cell growth and proliferation. Pathway analyses, including KEGG and Gene Set Enrichment Analysis (GSEA), indicated NEK2's association with established pathways like the cell cycle, and intriguingly, identified the circadian rhythm as a novel pathway influenced by NEK2. RNA sequencing data demonstrated NEK2's circadian rhythmic expression, and subsequent in vitro experiments confirmed its oscillation in synchronized ESCC cells. Moreover, we found a positive correlation between the efficacy of the NEK2 inhibitor INH6 and NEK2 expression levels in ESCC. In conclusion, our findings position NEK2 as a time-dependent oncogene and a potential biomarker in ESCC, highlighting its role in both tumorigenesis and the circadian rhythm.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CXCL9 and CXCL13 shape endometrial cancer immune-activated microenvironment via tertiary lymphoid structure formation.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-17 DOI: 10.1111/cas.16371

Yoshihiro Nagase, Makoto Kodama, Eriko Aimono, Kohei Nakamura, Reika Takamatsu, Keiko Abe, Takuma Yoshimura, Tatsuyuki Chiyoda, Wataru Yamagami, Hiroshi Nishihara

{"title":"CXCL9 and CXCL13 shape endometrial cancer immune-activated microenvironment via tertiary lymphoid structure formation.","authors":"Yoshihiro Nagase, Makoto Kodama, Eriko Aimono, Kohei Nakamura, Reika Takamatsu, Keiko Abe, Takuma Yoshimura, Tatsuyuki Chiyoda, Wataru Yamagami, Hiroshi Nishihara","doi":"10.1111/cas.16371","DOIUrl":"https://doi.org/10.1111/cas.16371","url":null,"abstract":"Immune checkpoint inhibitor (ICI) therapy has been successfully applied to various cancers; however, not all patients respond to ICI therapy. Tumors with an immune-activated environment are highly responsive to ICIs. To identify the cells and molecules essential to the formation of an immune-activated cancer microenvironment, we focused on the tertiary lymphoid structure (TLS) and performed histological and genomic analyses using endometrial cancer material. In the high immunogenic group, numerous TLSs were observed, and CXCL9 and CXCL13 expression was markedly increased. CXCL9-positive antigen-presenting and CXCL13-positive follicular dendritic cells were distributed in the T- and B-cell zones of TLSs, respectively. A group of molecules whose expression was upregulated along with CXCL9 and CXCL13 expression was strongly associated with cellular immunity. These results suggest that CXCL9-expressing antigen-presenting cells and CXCL13-expressing follicular dendritic cells coordinately shape the immune-activated microenvironment through TLS formation. The current findings will contribute to a better understanding of the mechanisms underlying the activated cancer immune microenvironment, thereby advancing the field of precision cancer medicine.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SPOP Suppresses Hepatocellular Carcinoma Growth and Metastasis by Ubiquitination and Proteasomal Degradation of TRAF6.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-17 DOI: 10.1111/cas.70025

Wenyi Chang, Kaiying Feng, Peng Zhou, Deao Gong, Ke Wang, Ailong Huang, Kai Wang, Ni Tang

{"title":"SPOP Suppresses Hepatocellular Carcinoma Growth and Metastasis by Ubiquitination and Proteasomal Degradation of TRAF6.","authors":"Wenyi Chang, Kaiying Feng, Peng Zhou, Deao Gong, Ke Wang, Ailong Huang, Kai Wang, Ni Tang","doi":"10.1111/cas.70025","DOIUrl":"https://doi.org/10.1111/cas.70025","url":null,"abstract":"Tumor necrosis factor receptor-associated factor-6 (TRAF6) is a well-established upstream regulator of the IKK complex, essential for the modulation of the NF-κB (nuclear factor kappa B) signaling pathway. Aberrant activation of TRAF6 has been strongly implicated in the pathogenesis of various cancers, including hepatocellular carcinoma (HCC). The speckle type BTB/POZ protein (SPOP), an E3 ubiquitin ligase substrate-binding adapter, constitutes a significant component of the CUL3/SPOP/RBX1 complex, which is closely linked to tumorigenesis. In this study, we demonstrated that the E3 ubiquitin ligase SPOP shielded TRAF6 from proteasomal degradation, leading to the hyperactivation of the NF-κB pathway. Notably, a liver cancer-associated S119N mutation in SPOP resulted in a failure to mediate the ubiquitination and subsequent degradation of TRAF6. Moreover, both gain-of-function and loss-of-function experiments revealed that SPOP inhibits the proliferation and invasion of HCC cells through the TRAF6-NF-κB axis in vitro and in vivo. Taken together, our findings elucidate the underpinning mechanism by which SPOP negatively regulates the stability of the TRAF6 oncoprotein, thus offering a new therapeutic target for HCC intervention.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143442542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Role of IL-34 in Tumors and Its Application to Regulate Inflammation.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-14 DOI: 10.1111/cas.70020

Yuichi Igarashi, Ken-Ichiro Seino

{"title":"Role of IL-34 in Tumors and Its Application to Regulate Inflammation.","authors":"Yuichi Igarashi, Ken-Ichiro Seino","doi":"10.1111/cas.70020","DOIUrl":"https://doi.org/10.1111/cas.70020","url":null,"abstract":"Interleukin (IL)-34 is a relatively recently discovered cytokine which binds to colony-stimulating factor-1 receptor (CSF-1R). So far, there has been no clear explanation as to why CSF-1R requires two ligands. While CSF-1 is ubiquitously expressed, the expression of IL-34 is relatively restricted. However, it has been revealed that IL-34 expression increases in various diseases and is associated with their pathology. Naturally, both IL-34 and CSF-1 stimulate CSF-1R, thereby contributing to the differentiation of monocytes into macrophages. In many cases, the induced macrophages significantly influence the disease pathology. In particular, we have demonstrated that IL-34 expression in cancer is deeply involved in tumor progression and therapeutic resistance. We have shown that the blockade of IL-34 significantly improved therapeutic efficacy such as chemotherapy, radiotherapy, and immune checkpoint blockade against IL-34-expressing cancers. Recently, since macrophages induced by IL-34 exhibit immunosuppressive properties, whereas IL-34 can enhance inflammation, there is growing interest in actively regulating inflammation utilizing IL-34. In this review article, we provide an overview of the characteristics and roles of IL-34 and discuss how it could be applied to future diagnostics and therapeutics.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Mutual Interaction Between GSTP1 and p53 Improves the Drug Resistance and Malignant Biology of Pancreatic Cancer.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-14 DOI: 10.1111/cas.70019

Guosen Wang, Yi Cao, Tengcheng Hu, Zhengqing Cai, ChuanPing Chen, Qilong Geng, Xinyu Luo, Yang Liu, Weijie Wang, Jiabin Jin, Weiwei Sheng

{"title":"A Mutual Interaction Between GSTP1 and p53 Improves the Drug Resistance and Malignant Biology of Pancreatic Cancer.","authors":"Guosen Wang, Yi Cao, Tengcheng Hu, Zhengqing Cai, ChuanPing Chen, Qilong Geng, Xinyu Luo, Yang Liu, Weijie Wang, Jiabin Jin, Weiwei Sheng","doi":"10.1111/cas.70019","DOIUrl":"https://doi.org/10.1111/cas.70019","url":null,"abstract":"Glutathione S-transferase P1 (GSTP1), a classic tumor biomarker, plays a controversial role in cancer progression. However, its specific role in pancreatic cancer (PC) has rarely been investigated. In the present study, we investigated the function and relationship between GSTP1 and mutant/wild-type p53 (mtp53/wtp53) in PC in vitro and in vivo. Compared with paired adjacent normal pancreas tissue, GSTP1 was downregulated in PC tissue, which was closely correlated with lymph node metastasis, Union for International Cancer Control (UICC) stage, and a better outcome of PC patients, processes dependent on wtp53 rather than mtp53. Moreover, a mutual regulation between GSTP1 and p53 was found in wtp53 PC cells. GSTP1 overexpression inhibited cell proliferation and chemotherapy resistance in vitro via wtp53/p21 and Bax/Bcl2 signaling, which was significantly reversed by wtp53 silencing, and vice versa. Similarly, the coordination of GSTP1 and p53 regulated the invasion and migration of PC cells, which was accompanied by changes in epithelial-mesenchymal transition (EMT) signaling (E-cad, ZO-1 and MMP9). Moreover, GSTP1 overexpression inhibited tumor growth and liver metastasis in vivo, as did high wtp53 and low ki67 expression. Interestingly, GSTP1 did not coimmunoprecipitate with either mtp53 or wtp53 in vitro. However, the wtp53 protein, as a transcription factor, could bind to the GSTP1 DNA promoter to transactivate GSTP1 mRNA expression as demonstrated via a Chip assay. Additionally, GSTP1 promoted the translocation of wtp53 into the nucleus but not mtp53. These results suggest that the positive feedback regulation of GSTP1 and wtp53 plays a significant role in cell proliferation, drug resistance, cell invasion and metastasis in PC.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-13 DOI: 10.1111/cas.70022

Kosuke Yoshida, Akira Yokoi, Hironori Suzuki, Satoshi Tamauchi, Masami Kitagawa, Eri Inami, Jun Nakayama, Yutaro Mori, Koji Okamoto, Yutaka Suzuki, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto

{"title":"Single-Nucleus RNA Sequencing and Spatial Transcriptomics for Squamous Cell Carcinoma Arising From Ovarian Mature Teratoma.","authors":"Kosuke Yoshida, Akira Yokoi, Hironori Suzuki, Satoshi Tamauchi, Masami Kitagawa, Eri Inami, Jun Nakayama, Yutaro Mori, Koji Okamoto, Yutaka Suzuki, Hiroshi Yoshida, Tomoyasu Kato, Hiroaki Kajiyama, Yusuke Yamamoto","doi":"10.1111/cas.70022","DOIUrl":"https://doi.org/10.1111/cas.70022","url":null,"abstract":"Squamous cell carcinoma arising from mature teratoma (SCC-MT) is a rare ovarian malignancy. The detailed molecular pathology of SCC-MT is not well understood. Moreover, the prognosis of the patients remains poor because no standard treatment has been established. In this study, we performed single-nucleus RNA sequencing and spatial transcriptomics using clinical SCC-MT samples to identify novel therapeutic candidates. snRNA-seq revealed three epithelial cell clusters, of which one was significantly associated with epidermis and keratinocyte development. Moreover, spatial transcriptomics revealed that the epithelial-mesenchymal transition was significantly inhibited, and the MYC and E2F targets were significantly activated in cancer spots on specimen sections. We focused on KLF5, which was one of the upregulated genes in cancer cells, and performed a functional analysis using NOSCC-1, a cell line derived from an SCC-MT. KLF5 downregulation significantly decreased cell proliferation and increased apoptosis. Furthermore, we previously identified miR-145-5p as a downregulated miRNA in SCC-MT. We demonstrated that miR-145-5p overexpression attenuated cell proliferation and decreased KLF5 expression. In conclusion, through multi-omics analyses, we identified unique gene expression profiles of SCC-MT and determined a role for KLF5 in SCC-MT development. Therefore, KLF5-related factors may be novel therapeutic targets, and further studies are needed to improve the diagnosis and treatment of SCC-MT.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mefloquine Suppresses Metastasis in Renal Cell Carcinoma Through Targeting SPC25.

IF 5.7 2区医学

Cancer Science Pub Date : 2025-02-13 DOI: 10.1111/cas.70001

Yongbo Wang, He Wang, Yipeng Xu, Jiawei Ling, Chuhong Zong, Yan Zhang, Xiaoxuan Guo, Guanan Zhao, Yuan Zhou, Jiahui Zhao, Pengrong Lou, Xigao Liu, Tengfei Xu, Qi Ma

{"title":"Mefloquine Suppresses Metastasis in Renal Cell Carcinoma Through Targeting SPC25.","authors":"Yongbo Wang, He Wang, Yipeng Xu, Jiawei Ling, Chuhong Zong, Yan Zhang, Xiaoxuan Guo, Guanan Zhao, Yuan Zhou, Jiahui Zhao, Pengrong Lou, Xigao Liu, Tengfei Xu, Qi Ma","doi":"10.1111/cas.70001","DOIUrl":"https://doi.org/10.1111/cas.70001","url":null,"abstract":"Renal cell carcinoma (RCC) is the third most common malignant tumor in the urinary system, often presenting with distant metastases at diagnosis. Approximately one-quarter of patients undergoing nephrectomy experience distant recurrence. Despite the recent advancements in combination-targeted and immune checkpoint inhibitor therapies, the development of new therapeutic strategies and the identification of biomarkers for metastatic risk remain crucial. The study found that high SPC25 expression is closely associated with poor clinical outcomes, and knocking down SPC25 significantly inhibits tumor cell proliferation and migration. Non-targeted metabolomics analysis also revealed that SPC25 knockdown reduces tumor cell activity, resulting in a low-invasive state. Additionally, this study utilized high-throughput molecular docking to screen small molecule drugs targeting SPC25, aiming to find drugs that inhibit RCC metastasis. The research discovered that mefloquine, at concentrations that do not significantly kill tumor cells, can markedly inhibit RCC metastasis. It was the first to report that mefloquine achieves its anti-metastatic effects by binding to SPC25 and inhibiting epithelial-mesenchymal transition. These results suggest that SPC25 has the potential to serve as an early biomarker for metastatic risk in RCC and highlight a novel strategy where mefloquine inhibits RCC metastasis through SPC25 binding, offering new avenues to improve the prognosis of RCC patients.","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0